Abstract

Background: Nephropathiaepidemica (NE) caused by Puumalahantavirus is a mild type of hemorrhagic fever with renal syndrome (HFRS). An immune-mediated pathogenesis is discussed for NE. Catabolism of tryptophan (Trp) along the kynurenine (Kyn) pathway is dependent on indoleamine 2,3-dioxygenase (IDO), an enzyme whose activity is induced during immune responses. Because viral infections can induce strong immune responses, we wanted to analyse whether there is a correlation between the severity of HFRS and Kyn or Trp serum concentration. Methods: We retrospectively studied 60 patients hospitalised with acute Puumalahantavirus infection during an epidemic in Germany in the year 2012. The infection was confirmed by positive antihantavirus IgG and IgM serum antibody. Plasma levels of Kyn and Trp were measured by mass spectrometry on admission in the hospital. Based on median glomerular filtration rate (GFR 32 mL/min/1.73 m2), patients were divided into two groups: with mild (n=21) and severe disease (n=39). Results: Serum Kyn and Kyn/Trp ratios were significantly higher (p<0.0001) in hantavirus-infected patients than in healthy controls. Patients with severe disease had a longer hospital stay than patients with mild disease (p=0.001) and their serum CRP (p=0.004), Kyn (p<0.001) and Kyn/Trp (p=0.001) ratios were significantly higher than those of patients with mild disease. Sensitivity and specificity, as well as logistic regression analysis showed that among the analysed parameters serum Kyn level was the most sensitive and specific inflammatory marker associated with renal function.

Conclusion: High serum Kyn concentrations in patients with NE caused by Puumalahantavirus are associated with a severe course of disease.

Keywords: HFRS; Hantavirus; IDO; Kynurenine; Tryptophan

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